Acetic Acid → tert-Butyl 4-[(4-acetylpiperazin-1-yl)methyl]-6-methylpyridin-2-ylcarbamate

HRID 1814017Notes

Reaction equation

HRID 1814017 reaction equation
[CH:1]([C:3]1[CH:8]=[C:7]([CH3:9])[N:6]=[C:5]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:4]=1)=O.[C:18]([N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1)(=[O:20])[CH3:19].CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl>[C:18]([N:21]1[CH2:26][CH2:25][N:24]([CH2:1][C:3]2[CH:8]=[C:7]([CH3:9])[N:6]=[C:5]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:4]=2)[CH2:23][CH2:22]1)(=[O:20])[CH3:19]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 837951-AcetylpiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 22504283Tert-butyl 4-formyl-6-methylpyridin-2-ylcarbamate

Product 1

HCID 22504317tert-Butyl 4-[(4-acetylpiperazin-1-yl)methyl]-6-methylpyridin-2-ylcarbamate

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

2-Chloro-6-methyl-pyridine-4-carbaldehyde (13-2, 0.609 g, 3.91 mmol), tert-butylcarbamate (0.550 g, 4.70 mmol), cesium carbonate (1.91 g, 5.87 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.036 g, 0.040 mmol) and Xantphos (0.068 g, 0.030 mmol) were stirred in 10 mL of anhydrous dioxane under N2. The reaction was heated to 80° C. and after 18 hours the reaction was cooled to room temperature. The mixture was diluted with water and extracted 3× with EtOAc. The extracts were dried over Na2SO4, filtered and concentrated. Purification by flash column chromatography afforded impure tert-butyl 4-formyl-6-methylpyridin-2-ylcarbamate. This aldehyde was dissolved in 2 mL of 1,2-dichloroethane. N-Acetylpiperazine (0.074 g, 0.58 mmol) was added followed by addition of 0.05 mL HOAc and NaBH(OAc)3 (0.122 g, 0.58 mmol). After 3 hours the reaction was quenched by the addition of half-saturated NaHCO3 (aq). The mixture was extracted 3× with DCM (dichloromethane) and the extracts were dried over Na2SO4, filtered and concentrated to afford the titled compound, 13-3. 1H NMR (CDCl3) δ 7.67 (s, 1H), 7.47 (s, 1H), 6.84 (s, 1H), 3.64 (t, 2H, J=4.9 Hz), 3.47 (m, 4H), 2.44 (m, 7H), 2.09 (s, 3H), 1.51 (s, 9H).

Workup

  1. customAfter 3 hours the reaction was quenched by the addition of half-saturated NaHCO3 (aq)
  2. extractionThe mixture was extracted 3× with DCM (dichloromethane)
  3. dry with materialthe extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-09e8eb6ab14e4e2eb5135c28419d8ad2
Source dataset
uspto-grants-2005_04
Patent number
US06875767B2

Reaction notes

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